"Gingivitis", as used herein, means inflammation of the gingiva (gums); it is often due to infection. Gingivitis is usually caused by the build-up of plaque, a sticky deposit of bacteria, mucous, food particles and other irritants, around the base of the teeth. It is believed that toxins produced by bacteria within the plaque irritate the gums, causing the gums to become infected, tender, and swollen. Gingivitis can also result from injury to the gums, usually from over vigorous tooth brushing or careless flossing.
Periodontitis", as used herein, means inflammation of the periodontium (the tissues that support the teeth). Chronic periodontitis is a complication of untreated gingivitis. If gingivitis is neglected, inflamed gum tissue at the base of the teeth becomes damaged and pockets form between the gums and the teeth. Plaque then collects in these pockets. The bacteria in the plaque attack the periodontal tissues, causing them to become inflamed and detached from the teeth. In advanced stages, the bacteria eventually erode the bones surrounding the teeth. However, as used herein, periodontitis is limited to the soft tissue (non-bone) aspects of the disease.
Histamine is a chemical present in cells throughout the body that is released during an allergic reaction and in instances of chronic inflammation. Histamine is one of the substances responsible for the symptoms of inflammation. It also stimulates production of acid by the stomach and narrows the bronchi (airways) in the lungs.
The effects of histamine can be counteracted by antihistaminic drugs, of which there are two well-known classes: histamine-1 receptor antagonists (H-1 antagonists) and histamine-2 receptor antagonists (H-2 antagonists). H-1 antagonists drugs are commonly used for treatment of a number of inflammatory conditions including hives and other rashes to relieve itching, swelling and redness, allergic rhinitis to relieve sneezing and runny nose, colds to dry up nasal secretions, and cough. Common H-1 antagonist drugs include chlorpheniramine, diphenhydramine, promethazine, terphenadine, trimeprazine and triprolidine.
References which disclose the use of various H-1 antagonists in oral care products or for treatment of various oral conditions are disclosed in the following references: U.S. Pat. No. 3,574,859 issued to Kosti on Apr. 13, 1971; U.S. Pat. No. 3,822,349 issued to Kosti on Jul. 2, 1974; U.S. Pat. No. 3,832,460 issued to Kosti on Aug. 27, 1974; U.S. Pat. No. 3,839,522 issued to Kosti on Oct. 1, 1974; U.S. Pat. No. 4,256,743 issued to Goldhaber on Mar. 17, 1981; U.S. Pat. No. 4,569,837 issued to Suzuki, Ikura, Noguchi, Izumizawa and Kinoshita on Feb. 11, 1986; U.S. Pat. No. 4,933,182 issued to Higashi, Kametaka, Izumi, Morisaki and Hayashi on Jun. 12, 1990; European Patent Application No. 0,241,179 of Rohto Pharmaceutical Company, published Oct. 14, 1987; European Patent Application No. 0,256,566 of ISCOFAR, published Feb. 24, 1988; European Patent Application No. 0,349,657 of Thornfeldt and Thornfeldt, published Jan. 10, 1990; British Patent Specification No. 1,045,031 of Kawakami, published Oct. 5, 1966; Canadian Patent No. 950,833 of Kosti, issued Jul. 9, 1974; Nakamoto, T., M. McCroskey and H. M. Mallek, "The Role of Ascorbic Acid Deficiency in Human Gingivitis--A New Hypothesis", J. Theor. Biol., Vol. 108 (1984), pp. 163-171; and Pernsteiner, C. L. and M. M. Ash, "Effect of Topical Application of Phenylephrine Hydrochloride on Hyperplastic Gingivitis", J. Periodontol., Vol. 48 (1977), pp. 473-477.
H-2 antagonists have not generally been found useful for treatment of inflammatory conditions. Instead, they are extensively used as drugs for preventing release of acid in the stomach to promote the healing of peptic ulcers and to relieve symptoms of esophagitis. Examples of well-known H-2 antagonist drugs include cimetidine, ranitidine and famotidine.
PCT Patent Application No. WO 89/04178 of Aktiebolaget Hassle, published May 18, 1989, discloses the use of H-2 antagonists for treatment of bone diseases, including the bone loss resulting from periodontal disease. The disclosed utility is achieved through systemic dosing of the H-2 antagonists. It is an object of the subject invention to provide a topical, oral treatment for gingivitis and soft tissue aspects of periodontitis.